title: Synthesis of some pyrazolyl benzenesulfonamide derivatives as dual anti-inflammatory antimicrobial agents.
abstract: Four series of pyrazolylbenzenesulfonamide derivatives were synthesized and evaluated for their anti-inflammatory activity using cotton pellet induced granuloma and carrageenan-induced rat paw edema bioassays. Moreover, COX-1 and COX-2 inhibitory activity, ulcerogenic effect and acute toxicity were also determined. Furthermore, the target compounds were screened for their in-vitro antimicrobial activity against Eischerichia coli, Staphylococcus aureus and Candida albicans. Compounds 4-(3-Phenyl-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide 9a and 4-(3-Tolyl-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide 9b were not only found to be the most active dual anti-inflammatory antimicrobial agents in the present study with good safety margin and minimal ulcerogenic effect but also exhibited good selective inhibitory activity towards COX-2. A docking pose for 9a and 9b separately in the active site of the human COX-2 enzyme was also obtained. Therefore, these compounds would represent a fruitful matrix for the development of dual anti-inflammatory antimicrobial candidates with remarkable COX-2 selectivity.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt. adnbekhit@hotmail.com
authors.forename: Adnan A
authors.initials: AA
authors.lastname: Bekhit
authors.forename: Hayam M A
authors.initials: HM
authors.lastname: Ashour
authors.forename: Alaa El-Din A
authors.initials: Ael-D
authors.lastname: Bekhit
authors.forename: Hamdy M
authors.initials: HM
authors.lastname: Abdel-Rahman
authors.forename: Salma A
authors.initials: SA
authors.lastname: Bekhit
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis*; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D002176:Candida albicans / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D000096926:Benzenesulfonamides